DESCRIPTION: The auditory cortex in the adult is now known to be dynamically regulated, in contrast to the traditional belief that it is physiologically static. A major regulatory factor is the learned behavioral importance of sound. Learning modifies the processing of frequency information and does so in a way that specifically emphasizes the frequency of a behaviorally acquired important stimulus. This conclusion is based on findings in both humans and animals of increased metabolic response to that stimulus, increased area representing that stimulus and shifts in the frequency tuning of cells to that stimulus. Such tuning changes are associative, highly frequency specific, develop rapidly and last indefinitely. Thus, the functional organization of the auditory cortex reflects both the physical parameters of sound and their acquired behavioral importance. The mechanisms of this dynamic regulation are virtually unknown. Two major candidates are (a) the covariance of pre- and post-synaptic levels of neuronal activity in the auditory cortex and (b) the neuromodulatory action of acetylcholine (ACh) on the auditory cortex. Specifically, in adult guinea pigs, we will (1) control postsynaptic response during tone presentation by nano-currents through a juxtacellular micropipette, (2) pair tone presentation with stimulation of nucleus basalis, the source of ACh to the auditory cortex, (3) block cholinergic actions of the auditory cortex during behavioral learning, (4) control postsynaptic response during tome in the presence of nucleus basalis stimulation and (5) determine the effects on various cell layers of the auditory cortex. The studies have important implications for health. The auditory cortex is essential for normal perception, particularly for speech, which is learned. Understanding the mechanisms of cortical plasticity using simple stimuli, i.e., pure tones, constitutes an entry point into the larger problem of cortical processing of complex stimuli, such as speech sounds. Additionally, this project will provide a basis for understanding learning to perceive speech following cochlear implants in the deaf and recently identified learning-based remediation of temporal processing deficits in dyslexia.